This investigation represents a continuous effort to elucidate the pathomechanism responsible for the greater susceptibility of adult than young animals to cerebral ischemia. Specifically, this study was concerned with the relationship between synaptosomal 5-hydoxytryptamine (5-HT) release and the kinetic properties of 5-HT2- (S2) postsynaptic receptors in the cerebral cortex of adult and young Mongolian gerbils subjected to the same ischemic insult (bilateral ischemia [15 min] with and without recirculation [60 min]). The results show a close correlation between the synaptosomal 5-HT release (= presynaptic function) and properties of 5-HT2-postsynaptic receptors in ischemia of adult and young gerbils. Only the increased release of 5-HT from synaptosomes modulated the profile of 5-HT2-postsynaptic receptors. These findings also suggest that the observed greater susceptibility of adult gerbils to brain ischemia than that of the young animals is linked to their distinctive neuronal function.